The overall goal of this University of Texas M.D. Anderson Cancer Center SPORE in Skin Cancer is to facilitate innovative research in the prevention, detection and treatment of melanoma leading to the elimination of this disease. This SPORE will achieve this goal by assembling a talented group of clinical and laboratory scientists who are committed to the translation of findings specific for melanoma from the lab to the clinic as well as from the clinic to the laboratory. The University of Texas M.D. Anderson Cancer Center has made as one of its priorities the elimination of melanomas as a health risk, and to this end, established in 1998 a Multidisciplinary Research Program in Melanoma to support training and research across traditional administrative boundaries in order to advance treatment of patients with melanoma. With this support, we have successfully organized an efficient and productive infrastructure that is the framework for this SPORE application. We are now poised to take advantage of the rapid increases in our understanding of melanoma at the molecular and cellular levels. Through this SPORE in Skin Cancer, we will enhance the translation of insights gleaned from research in melanoma biology and epidemiology to more effective prevention, detection and treatment approaches. This SPORE in Skin Cancer proposes five translational research projects, three career development positions and at least four developmental research awards all being served by three cores (Administrative; Informatics, Tissue Resource, and Pathology; and Biostatistics). The five projects address MHC-II-presented melanoma peptides engineered for optimal immunogenicity for CD4 cell activation (Project 1); molecular epidemiology of DNA repair enzyme function, genetics, and risk (Project 2); evaluation of inducible nitric oxide synthase as a prognostic factor for survival and exploration of signaling cascades for therapy (Project 3); regulation of IL-8 and MUC18/MCAM in combination with conventional chemotherapy as therapeutic approaches (Project 4); and evaluation of specific class II HLA alleles as prognostic factors for survival and evaluation of the role of associated cytokines in disease progression (Project 5). Through this research program and with the full support of the University of Texas, M.D. Anderson Cancer Center, we will make significant impact toward the prevention and detection of malignant melanoma processes, and treatment of patients with melanoma.